Potent nonpeptide endothelin antagonists: synthesis and structure–activity relationships of pyrazole-5-carboxylic acids

We have previously reported the identification of pyrazole-5-carboxylic acids as a new class of endothelin antagonists from low affinity pyrazol-5-ol ligands, which were obtained by random screening assays.1 We describe herein the synthesis and the structure–activity relationships (SARs) of these pyrazole-5-carboxylic acids with potent ETA selective, mixed ETA/ETB or moderately ETB selective antagonist activities.